GUEST LECTURES
Dr. Chang-Keun Lim
Assistant Professor
Department of Chemical and Material Engineering
School of Engineering and Digital Sciences
Nazarbayev University
Inflammation-responsive inflatable nanogels
for ultrasound molecular imaging
Abstract
Microbubbles are clinically used as an imaging agent for contrast-enhanced ultrasound image. Beyond the
preformed microbubbles, nanoscale gas-generating chemical systems that are capable of stimulus-
responsive inflation to microbubbles have recently been employed as a new echogenic strategy for
ultrasound molecular imaging. In this presentation, a peroxamide-based ultrasound contrast agent as a
hydrogen peroxide (H 2 O 2 , a reactive oxygen species with longest lifetime)-responsive gas (CO 2 )-generating
system for diagnostic ultrasound imaging of inflammatory diseases is introduced and demonstrated. A
hydrolytic degradation-resistant peroxamide nanogel is constructed by nanoscopic cross-linking of
polymeric aliphatic amines (branched polyethyleneimine) with oxalyl chloride, which intrinsically offers
highly concentrated peroxamides as a reactive cross-linking point for H 2 O 2 -responsive CO 2 -generation by
the peroxalate chemiluminescence reaction that is intrinsically catalyzed by the polyamine-derived
intraparticle basic environment. It is experimentally revealed that the interior of the peroxamide-
concentrated nanogel colloid serves as an optimal nanoscale catalytic reactor for the H 2 O 2 -responsive gas
generation as well as a gas reservoir capable of nano-to-micro inflation. We demonstrate that the
peroxamide-concentrated nanogels are indeed capable of enhancing the ultrasound contrast in response to
H 2 O 2 , which allows us to perform diagnostic ultrasound imaging of H 2 O 2 -overproducing inflammatory
diseases in mouse models. Along with the biocompatibility of the peroxamide nanogels revealed by the
animal toxicity study, our design strategy for the inflatable nanoparticles would contribute to the
advancement of activatable contrast agents for ultrasound molecular imaging.
References
1. C.-K. Lim et al., Rational design of inflammation-responsive inflatable nanogels for ultrasound
molecular imaging. Chem. Mater. 31 (2019) 2905-2912.
2. C.-K. Lim et al., Chemiluminescence-generating nanoreactor formulation for near-infrared
imaging of hydrogen peroxide and glucose level in vivo. Adv. Funct. Mater. 20 (2010) 2644-2648.